Skip to main content

Advertisement

SpringerLink
Log in

Effectiveness of the pharmacological treatments for sialorrhea in patients with Parkinson’s disease: a systematic review and network meta-analysis

  • Review
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

The present systematic review and network meta-analysis of randomized control trials (RCTs) aimed to establish whether there are evidence-based differences in the pharmacological agents used to manage sialorrhea in patients with Parkinson’s disease (PD).

Material and methods

The authors searched the databases: MEDLINE via PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library for clinical trials. Unpublished trials were searched on clinicaltrials.gov and the Brazilian Clinical Trials Registry. Means and standard deviations of changes in the salivary flow or drooling reported by participants due to the interventions were recorded.

Results

The authors analyzed 13 RCTs. Compared to the placebo, types A and B of the botulinum toxin effectively reduced the salivary flow and the severity or frequency of drooling. However, the network meta-analysis did not differentiate between the botulinum toxin types. Ipratropium bromide and glycopyrrolate did not differ from the placebo. Indirect evidence showed that ipratropium had similar results to those obtained with both types of botulinum toxin. The CINeMA approach estimated the quality of the evidence as very low for all comparisons.

Conclusion

The best treatment for sialorrhea in patients with PD is not fully elucidated yet. Therefore, more well-conducted randomized clinical trials are required to increase the level of evidence.

Clinical relevance

There needs to be more evidence defining the best intervention to treat sialorrhea in patients with PD. However, botulinum toxin types A and B seem to reduce sialorrhea in patients effectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

Data availability

The data supporting this study’s findings are available from the corresponding author, P.C.L., upon reasonable request.

References

  1. Dexter DT, Jenner P (2013) Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med 62:132–144. https://doi.org/10.1016/j.freeradbiomed.2013.01.018

    Article  PubMed  Google Scholar 

  2. Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T (2016) The incidence of Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology 46:292–300. https://doi.org/10.1159/000445751

    Article  PubMed  Google Scholar 

  3. Hayes MT (2019) Parkinson’s disease and Parkinsonism. Am J Med 132:802–807. https://doi.org/10.1016/j.amjmed.2019.03.001

    Article  PubMed  Google Scholar 

  4. Armstrong MJ, Okun MS (2020) Diagnosis and treatment of parkinson disease: a review. JAMA 323(6):548–560. https://doi.org/10.1001/jama.2019.22360

    Article  PubMed  Google Scholar 

  5. Van Wamelen DJ, Leta V, Johnson J, Ocampo CL, Podlewska AM, Rukavina K, Rizos A, Martinez-martin P, Chaudhuri KR (2020) Drooling in Parkinson’s disease: prevalence and progression from the non-motor international longitudinal study. Dysphagia 35:955–961. https://doi.org/10.1007/s00455-020-10102-5

    Article  PubMed  PubMed Central  Google Scholar 

  6. Jost WH, Steffen A, Steffen B (2021) A critical review of incobotulinumtoxinA in the treatment of chronic sialorrhea in pediatric patients. Expert Rev Neurother 21(10):1059–1068. https://doi.org/10.1080/14737175.2021.1979959

    Article  PubMed  Google Scholar 

  7. Srivanitchapoom P, Pandey S, Hallett M (2014) Drooling in Parkinson’s disease: a review. Parkinsonism Relat Disord 20:1109–1118. https://doi.org/10.1016/j.parkreldis.2014.08.013

    Article  PubMed  PubMed Central  Google Scholar 

  8. Isaacson J, Patel S, Torres-Yaghi Y, Pagán F (2020) Sialorrhea in Parkinson’s disease. Toxins (Basel) 12(11):691. https://doi.org/10.3390/toxins12110691

    Article  PubMed  Google Scholar 

  9. Mcgeachan AJ, Mcdermott CJ (2017) Management of oral secretions in neurological disease. Pract Neurol 17:96–103. https://doi.org/10.1136/practneurol-2016-001515

    Article  PubMed  Google Scholar 

  10. Tiigimäe-Saar J, Taba P, Tamme T (2017) Does Botulinum neurotoxin type A treatment for sialorrhea change oral health? Clin Oral Investig 21:795–800. https://doi.org/10.1007/s00784-016-1826-z

    Article  PubMed  Google Scholar 

  11. Sridharan K, Sivaramakrishnan G (2018) Pharmacological interventions for treating sialorrhea associated with neurological disorders: a mixed treatment network meta-analysis of randomized controlled trials. J Clin Neurosci 51:12–17. https://doi.org/10.1016/j.jocn.2018.02.011

    Article  PubMed  Google Scholar 

  12. Isaacson J, Patel S, Torres-yaghi Y, Pagán F (2020) Sialorrhea in Parkinson’s disease. Toxins (Basel) 12:691. https://doi.org/10.3390/toxins12110691

    Article  PubMed  Google Scholar 

  13. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, Ioannidis JP, Straus S, Thorlund K, Jansen JP, Mulrow C, Catalá-López F, Gøtzsche PC, Dickersin K, Boutron I, Altman DG, Moher D (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162:777–784. https://doi.org/10.7326/M14-2385

    Article  PubMed  Google Scholar 

  14. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (eds) (2011) Cochrane Handbook for systematic reviews of Interventions 5.1.0. Available at: https://handbook-5-1.cochrane.org/. Accessed 8 Nov 2021

  15. Steinlechner S, Klein C, Moser A, Lencer R, Hagenah J (2010) Botulinum toxin B as an effective and safe treatment for neuroleptic-induced sialorrhea. Psychopharmacology 207:593–597. https://doi.org/10.1007/s00213-009-1689-y

    Article  PubMed  Google Scholar 

  16. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT (2019) RoB 2: a revised tool for assessing the risk of bias in randomized trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898

    Article  PubMed  Google Scholar 

  17. Harrer M, Cuijpers P, Furukawa TA, Ebert DD (2021) Doing meta-analysis with R: a hands-on guide. CRC Press, Boca Raton

    Book  Google Scholar 

  18. Rücker G, Schwarzer G (2015) Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med Res Methodol 31(15):58. https://doi.org/10.1186/s12874-015-0060-8

    Article  Google Scholar 

  19. Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JP (2014) Evaluating the quality of evidence from a network meta-analysis. PLoS One 9:e99682. https://doi.org/10.1371/journal.pone.0099682

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nikolakopoulou A, Higgins JPT, Papakonstantinou T, Chaimani A, Del Giovane C, Egger M, Salanti G (2020) CINeMA: an approach for assessing confidence in the results of a network meta-analysis. CINeMA: an approach for assessing confidence in the results of a network meta-analysis. PLoS Med 17:e1003082. https://doi.org/10.1371/journal.pmed.1003082

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lipp A, Trottenberg T, Schink T, Kupsch A, Arnold G (2003) A randomized trial of botulinum toxin A for treatment of drooling. Neurology 61:1279–1281. https://doi.org/10.1212/wnl.61.9.1279

    Article  PubMed  Google Scholar 

  22. Mancini F, Zangaglia R, Cristina S, Sommaruga MG, Martignoni E, Nappi G, Pacchetti C (2003) Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism. Mov Disord 18:685–688. https://doi.org/10.1002/mds.10420

    Article  PubMed  Google Scholar 

  23. Ondo WG, Hunter C, Moore W (2004) A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in Parkinson’s disease. Neurology 62:37–40. https://doi.org/10.1212/01.wnl.0000101713.81253.4c

    Article  PubMed  Google Scholar 

  24. Lagalla G, Millevolte M, Capecci M, Provinciali L, Ceravolo MG (2006) Botulinum toxin type A for drooling in Parkinson’s disease: a double-blind, randomized, placebo-controlled study. Mov Disord 21:704–707. https://doi.org/10.1002/mds.20793

    Article  PubMed  Google Scholar 

  25. Thomsen TR, Galpern WR, Asante A, Arenovich T, Fox SH (2007) Ipratropium bromide spray as a treatment for sialorrhea in Parkinson’s disease. Mov Disord 22:2268–2273. https://doi.org/10.1002/mds.21730

    Article  PubMed  Google Scholar 

  26. Lagalla G, Millevolte M, Capecci M, Provinciali L, Ceravolo MG (2009) Long-lasting benefits of botulinum toxin type B in Parkinson’s disease-related drooling. J Neurol 256:563–567. https://doi.org/10.1007/s00415-009-0085-1

    Article  PubMed  Google Scholar 

  27. Arbouw ME, Movig KL, Koopmann M, Poels PJ, Guchelaar HJ, Egberts TC, Neef C, van Vugt JP (2010) Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 74:1203–1207. https://doi.org/10.1212/WNL.0b013e3181d8c1b7

    Article  PubMed  Google Scholar 

  28. Guidubaldi A, Fasano A, Ialongo T, Piano C, Pompili M, Mascianà R, Siciliani L, Sabatelli M, Bentivoglio AR (2011) Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson’s disease. Mov Disord 26:313–319. https://doi.org/10.1002/mds.23473

    Article  PubMed  Google Scholar 

  29. Chinnapongse R, Gullo K, Nemeth P, Zhang Y, Griggs L (2012) Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson’s disease: a prospective, double-blind trial. Mov Disord 27:219–226. https://doi.org/10.1002/mds.23929

    Article  PubMed  Google Scholar 

  30. Jost WH, Friedman A, Michel O, Oehlwein C, Slawek J, Bogucki A, Ochudlo S, Banach M, Pagan F, Flatau-Baqué B, Csikós J, Cairney CJ, Blitzer A (2019) SIAXI: placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea. Neurology 92:e1982–e1991. https://doi.org/10.1212/WNL.0000000000007368

    Article  PubMed  PubMed Central  Google Scholar 

  31. Isaacson SH, Ondo W, Jackson CE, Trosch RM, Molho E, Pagan F, Lew M, Dashtipour K, Clinch T, Espay AJ, MYSTICOL Study Group (2020) Safety and efficacy of rimabotulinumtoxinB for treatment of sialorrhea in adults: a randomized clinical trial. JAMA Neurol 77:461–469. https://doi.org/10.1001/jamaneurol.2019.4565

    Article  PubMed  PubMed Central  Google Scholar 

  32. Mestre TA, Freitas E, Basndwah A, Lopez MR, de Oliveira LM, Al-Shorafat DM, Zhang T, Lui JP, Grimes D, Fox SH (2020) Glycopyrrolate improves disability from sialorrhea in Parkinson’s disease: a 12-week controlled trial. Mov Disord 35:2319–2323. https://doi.org/10.1002/mds.28196

    Article  PubMed  Google Scholar 

  33. Krahn U, Binder H, König J (2013) A graphical tool for locating inconsistency in network meta-analyses. BMC Med Res Methodol 13:35. https://doi.org/10.1186/1471-2288-13-35

    Article  PubMed  PubMed Central  Google Scholar 

  34. Salanti G, Ades AE, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64:163–171. https://doi.org/10.1016/j.jclinepi.2010.03.016

    Article  PubMed  Google Scholar 

  35. Mbuagbaw L, Rochwerg B, Jaeschke R, Heels-Andsell D, Alhazzani W, Thabane L, Guyatt GH (2017) Approaches to interpreting and choosing the best treatments in network meta-analyses. Syst Rev 6(1):79. https://doi.org/10.1186/s13643-017-0473-z

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cohen J (1988) Statistical power analysis for the behavioral sciences. Routledge, Oxfordshire

    Google Scholar 

  37. Ruiz-Roca JA, Pons-Fuster E, Lopez-Jornet P (2019) Effectiveness of the botulinum toxin for treating sialorrhea in patients with parkinson’s disease: a systematic review. J Clin Med 8:317. https://doi.org/10.3390/jcm8030317

    Article  PubMed  PubMed Central  Google Scholar 

  38. Filho Oliveira AF, Silva GA, Almeida DM (2016) Application of botulinum toxin to treat sialorrhea in amyotrophic lateral sclerosis patients: a literature review. Einstein (Sao Paulo) 14:431–434. https://doi.org/10.1590/S1679-45082016RB3594

    Article  Google Scholar 

  39. Dashtipour K, Bhidayasiri R, Chen JJ, Jabbari B, Lew M, Torres-Russotto D (2017) RimabotulinumtoxinB in sialorrhea: systematic review of clinical trials. J Clin Mov Disord 4:9. https://doi.org/10.1186/s40734-017-0055-1

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hung SA, Liao CL, Lin WP, Hsu JC, Guo YH, Lin YC (2021) Botulinum toxin injections for treatment of drooling in children with cerebral palsy: a systematic review and meta-analysis. Children (Basel) 8:1089. https://doi.org/10.3390/children8121089

    Article  PubMed  Google Scholar 

Download references

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES, Finance Code 001).

Author information

Authors and Affiliations

  1. Graduate Program in Dentistry, Federal University of Sergipe, Rua Cláudio Batista, S/N, Sanatório, Aracaju, SE, 49.060-108, Brazil

    Luiz Carlos Santos Junior, André Luís Faria-e-Silva & Pollyana Caldeira Leal

  2. Behavioral and Evolutionary Neurobiology Laboratory, Department of Biosciences, Federal University of Sergipe, Av. Vereador Olímpio Grande, S/N, Itabaiana, SE, 49506-036, Brazil

    José Ronaldo Santos

  3. Department of Restorative Dentistry, State University of Ponta Grossa, Avenida Carlos Cavalcanti, 4748, Bloco M, Sala 04, Ponta Grossa, PR, 84030-900, Brazil

    Alessandra Reis

Authors
  1. Luiz Carlos Santos Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José Ronaldo Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandra Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. André Luís Faria-e-Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pollyana Caldeira Leal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: José Ronaldo dos Santos, Pollyana Caldeira Leal.

Methodology: Alessandra Reis.

Formal analysis and investigation: Luiz Carlos Santos Junior, Alessandra Reis, André Luís Faria-e-Silva, Pollyana Caldeira Leal.

Writing—original draft preparation: Luiz Carlos Santos Junior, José Ronaldo dos Santos, Alessandra Reis, André Luís Faria-e-Silva, Pollyana Caldeira Leal.

Writing—review and editing: Luiz Carlos Santos Junior, José Ronaldo dos Santos, Alessandra Reis, André Luís Faria-e-Silva, Pollyana Caldeira Leal.

Funding acquisition: Pollyana Caldeira Leal.

Resources: Pollyana Caldeira Leal.

Supervision: Pollyana Caldeira Leal.

Corresponding author

Correspondence to Pollyana Caldeira Leal.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 19 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santos Junior, L.C., Santos, J.R., Reis, A. et al. Effectiveness of the pharmacological treatments for sialorrhea in patients with Parkinson’s disease: a systematic review and network meta-analysis. Clin Oral Invest 27, 2449–2463 (2023). https://doi.org/10.1007/s00784-023-04981-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-023-04981-9

Keywords

Search

Navigation